Title: Design and Synthesis of New N1 and C3-Substituted 4-Fluoroindolic Melatoninergics
VOLUME: 4 ISSUE: 3
Author(s):Andrew Tsotinis, Andreas Eleutheriades, Kathryn Davidson, David Sugden, Andrew Tsotinis, Andreas Eleutheriades, Kathryn Davidson and David Sugden
Affiliation:Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Panepistimioupoli-Zografou, 157 71 Athens, Greece., Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Panepistimioupoli-Zografou, 157 71 Athens, Greece.
Keywords:Substituted 4-fluoroindoles, synthesis, melatoninergic activity
Abstract: A series of new C-3 and N1-substituted 4-fluorotryptamides have been prepared and tested for their ability to activate pigment granule aggregation in Xenopus laevis melanophores and bind to the recombinant human MT1 and MT2 melatonin receptor subtypes expressed in NIH 3T3 cells. Planar sp2 geometry at C-3-βC seems to decrease the population of the preferred conformation as it renders 4-fluoroindoles 4b-d weaker antagonists than their C-3-βC-unsubstituted congeners 3a-e. This effect is not preclusively linked with the C-3 region, as the same geometry around N1 (compounds 5a-c) similarly leads to weak antagonistic action. Last, the new C-3 substituted 4-fluorotryptamides presented herein are substantially more potent than their respective N-OMe functionalized congeners, previously reported.
